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The molecular structure of the polymer PM6 is elaborately modified through random copolymerization by incorporating simple units of either difluoro-substituted thiophene (2FT) or dicyano-substituted thiophene (2CNT). The incorporation of the 2FT unit significantly enhanced the coplanarity of the random copolymers, leading to improved molecular crystallinity, whereas the introduction of the 2CNT unit featured the opposite effect. Thanks to the optimized morphology resembling a fiber-like interpenetrating network structure, the organic solar cells based on PM6-10%2FT:IT4F showed higher and more balanced charge mobilities, achieving a power conversion efficiency (PCE) of 12.65%, which is comparable to that of PM6-based devices. For comparison, the 2CN-series random copolymers-based devices exhibited lower PCEs of Ë12%. Interestingly, a superior PCE close to 19.0% is achieved in PM6:L8-BO:PM6-20%2CN based ternary device due to the significant improvement in open-circuit voltage. This work demonstrates that the crystallinity of donor polymers can be enhanced by introducing simple structural units to strengthen the coplanarity of the backbone, thereby achieving an optimized morphology that promotes favorable charge transport.
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Aflatoxin B1 (AFB1) is one of the most harmful and toxic mycotoxins in foods and feeds, posing a serious health risk to both humans and animals, especially its hepatotoxicity. Nuclear factor-erythroid 2-related factor 2 (Nrf2), an important nuclear transcription factor, is generally recognized as a potential target for phytochemicals to ameliorate liver injury. The current study sought to elucidate the molecular processes by which licochalcone A (Lico A), a compound derived from Xinjiang licorice Glycyrrhiza inflate, protects against AFB1 toxicity. In vivo, male wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6 mice were orally administered AFB1 at 1.5 mg/kg body weight (BW) with or without Lico A at 5 mg/kg. In vitro, AML12 cells were utilized to evaluate the protective effect and mechanism of Lico A against the AFB1-induced hepatotoxicity. Our findings demonstrated that AFB1 caused severe hepatotoxicity, while Lico A treatment successfully relieved the toxicity. Meanwhile, Lico A effectively improved liver injury, inflammatory mediators, oxidative insults, apoptosis, liver fibrosis, and pyroptosis, which contributed to the inhibition of toll receptor 4 (TLR4)-NF-κB/MAPK and NOD-like receptors protein 3 (NLRP3)/caspase-1/GSDMD signaling pathway activation. Furthermore, Lico A was able to enhance the Nrf2 antioxidant signaling pathway. Intriguingly, Lico A still had a protective effect on AFB1-caused liver injury in mice via the inhibition of inflammation and pyroptosis, while apoptosis and liver fibrosis were blocked in the absence of Nrf2. To sum up, the present study first elucidated that Lico A ameliorated AFB1-induced hepatotoxic effects and its main mechanism involved the inhibitory effects on oxidative stress, apoptosis, liver fibrosis, inflammation, and pyroptosis, which might be partially dependent on the regulation of Nrf2. The work may enrich the role and mechanism of Lico A's resistance to liver injury caused by various factors, and its application is promising.
Assuntos
Chalconas , Doença Hepática Induzida por Substâncias e Drogas , Fator 2 Relacionado a NF-E2 , Humanos , Masculino , Animais , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Aflatoxina B1/toxicidade , Camundongos Endogâmicos C57BL , Transdução de Sinais , Estresse Oxidativo , Inflamação/metabolismo , Fígado/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cirrose Hepática/metabolismoRESUMO
Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1ß (IL-1ß), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.
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Gasderminas , Microbioma Gastrointestinal , Piroptose , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resposta ao Choque Frio , Proteínas de Ligação a Fosfato/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Íleo/metabolismo , Íleo/microbiologia , Íleo/patologia , Inflamação/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
Chronic cold exposure, which is the main inducer of lung diseases in high latitudes, affects production efficiency and restricts the development of aquaculture. Although the relationship between cold exposure and susceptibility to the lungs is widely accepted, but the influence between them has not been fully explored. The aim of this study is to understand the underlying mechanism. In the present study, the mice, which are used to establish cold stress (CS)-induced lung injury model, are exposed to cold temperature (4 °C) for 3 h each day for 4 weeks. The results indicate that the expression of heat shock protein 70 (HSP70) is augmented by cold exposure. In addition, chronic cold exposure aggravate the formation of malondialdehyde (MDA) and lead to a significant decrease in the contents of micrococcus catalase (CAT) and glutathione (GSH). Moreover, chronic cold exposure significantly exacerbates the expression of inflammation- and apoptosis-related proteins. The activation of Bax and caspase-3 are significantly augmented. However, that of Bcl-2 is decreased. These results are different from those in room team. The results show that chronic cold exposure plays an important roles in the activation of multiple signaling pathways, such as pyroptosis-related, inflammation-related and oxidative stress-regulated signaling pathways. In summary, these investigations support that chronic cold exposure increase the risk of lung injury by activating inflammation, oxidative stress and pyroptosis.
Assuntos
Lesão Pulmonar , Pneumonia , Camundongos , Animais , Piroptose , Estresse Oxidativo , Inflamação , GlutationaRESUMO
As innate immune effector cells in the central nervous system (CNS), microglia not only are essential for the normal development of nervous system but also act on different neurological diseases, including Alzheimer's disease (AD), Huntington's disease (HD), and other neuroinflammatory diseases. Mogroside V (Mog), a natural plant active ingredient and isolated form of Momordica grosvenori, has been shown to possess anti-inflammatory action, but few studies were carried out to investigate the effects of Mog on neuroinflammation. This study aimed to investigate the role of Mog in lipopolysaccharide- (LPS-) induced neuroinflammation and neuronal damage, revealing the underlying mechanisms. Our data indicated that Mog significantly inhibited the LPS-induced production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2 cells. We found that Mog also suppressed toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), the phosphorylation of mitogen-activated protein kinases (MAPKs), adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of γ-glutamyl cysteine synthetase catalytic subunit (GCLC), modifier subunit (GCLM), heme oxygenase-1 (HO-1), and quinine oxidoreductase 1 (NQO1) proteins, mostly depending on the nuclear translation of nuclear factor erythroid-2 related factor 2 (Nrf2). In contrast, pretreatment with inhibitors of AKT can suppress the phosphorylation of AMPK, Nrf2, and its downstream proteins expression. In summary, Mog might play a protective role against LPS-induced neurotoxicity by inhibiting the TLR4-MyD88 and activation of AMPK/AKT-Nrf2 signaling pathway.
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Parkinson's disease (PD) is a progressive neurodegenerative disorder that is closely associated with oxidative stress. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key transcription factor that regulates oxidative stress. Isoorientin (IOT), as a dietary C-glucosyl flavone derived from rooibos tea, cereals and legumes, is thought to possess multiple pharmacological activities; however, the protective effect of IOT against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells is still poorly understood. The present study focused on investigating whether IOT could ameliorate neurotoxicity and the underlying mechanisms. Our findings indicated that IOT significantly inhibited neurotoxicity reduced apoptotic cell numbers, reactive oxygen species (ROS) overproduction and mitochondrial membrane potential, and modulated the expression of apoptosis-related proteins, including Bcl-2, Bax and caspase-3, which were induced by 6-OHDA. Moreover, IOT also enhanced the expression of the GCLC, GCLM, HO-1, NQO1 and Trx-1 proteins, which mostly depends on the nuclear translation of Nrf2 and reduced expression of the Keap1 protein. IOT significantly increased the phosphorylation of AMPK, ERK, GSK3ß, JNK, PI3K and AKT. In contrast, pretreatment with the inhibitors of AMPK and PI3K/AKT only suppressed the nuclear translocation of Nrf2. In addition, the expression of these proteins was effectively decreased by 6-OHDA, and this effect was reversed by IOT treatment. Importantly, the effect of IOT on improving 6-OHDA induced neurotoxicity was remarkably abrogated by the application of Nrf2 siRNA and, AMPK and PI3K/AKT inhibitors. In summary, IOT might play a protective role against 6-OHDA-induced neurotoxicity by inducing the expression of various antioxidant enzymes via the activation of the AMPK/AKT-Nrf2 signalling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Oxidopamina/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Espécies Reativas de Oxigênio/metabolismoRESUMO
Binding of baicalein, wogonin and baicalin to fish sperm DNA was studied by using ethidium bromide dye as a fluorescence probe. To study the binding mechanism, the absorption, fluorescence, melting temperature and viscosity measurement were carried out. The experimental results indicated that the planar of flavonoids intercalated to the DNA helix. When bound to DNA, flavonoids showed hyperchromic and blue shift in the absorption spectra and fluorescence quenching (>50%) in the fluorescence spectra. Furthermore, the intercalative binding was consistent with the red shift in the position of λ max in the fluorescence spectra. It was also found that ionic strength had little or no effect on the binding of flavonoids and DNA. Stern-Volmer plots at 25 and 37 °C showed that the quenching of fluorescence by flavonoids was a combined quenching process. The binding site number n, apparent binding constant K A at 25 and 37 °C, and the corresponding thermodynamic parameters ΔG, ΔH, ΔS at 25 °C were obtained. The interaction of flavonoid-metal complexes with DNA was also studied by spectral methods, and the results suggested that the complexes intercalated into DNA.
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Emodin interacting with deoxyribonucleic acid (DNA) has been studied by different spectroscopic techniques, such as fluorescence, ultraviolet and visible (UV-vis), and fourier transform infared (FT-IR) spectroscopies, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system on addition of emodin shows that the fluorescence quenching of DNA-EB complex by emodin occurs. The binding constants of emodin with DNA in the presence of EB are 6.02x10(4), 9.20x10(4) and 1.17x10(5)Lmol(-1) at 20, 35 and 50 degrees C, respectively. FT-IR spectrum further suggests that both the phosphate groups and the bases of DNA react with emodin. The reaction of DNA with emodin in the presence of EB is affected by ionic strength and temperature. The values of melting temperature (T(m)) of DNA-EB complex and emodin-DNA-EB complexes were determined, respectively. From the experiment evidences, the major binding mode of emodin with DNA should be the groove binding.
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DNA/metabolismo , Emodina/metabolismo , Etídio/metabolismo , Animais , Desnaturação de Ácido Nucleico , Concentração Osmolar , Salmão , Espectrometria de Fluorescência , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Temperatura , TermodinâmicaRESUMO
The interactions of fish sperm deoxyribonucleic acid (DNA) with anthraquinones, such as chrysophanol, physcion and 1,8-dihydroxy anthraquinone, were investigated by using ethidium bromide (EB) as fluorescence probe. The binding constants of anthraquinones and DNA were obtained by the fluorescence quenching technique. Further, the binding mechanisms on the reaction of the three anthraquinones with DNA and effect of ionic strength on the fluorescence property of the system have also been investigated. The results of the assay indicate that the binding modes of chrysophanol, physcion and 1,8-dihydroxy anthraquinone with DNA were evaluated to be groove binding. And the binding constants of chrysophanol, physcion and 1,8-dihydroxy anthraquinone with DNA-EB complex were 1.64x10(4), 3.04x10(4) and 2.88x10(5) l mol(-1), respectively.